Sexually Dimorphic Response to Hepatic Injury in Newborn Suffering from Intrauterine Growth Restriction.

Intrauterine growth restriction (IUGR), when a fetus does not grow as expected, is associated with a reduction in hepatic functionality and a higher risk for chronic liver disease in adulthood. Utilizing early developmental plasticity to reverse the outcome of poor fetal programming remains an unexplored area. Focusing on the biochemical profiles of neonates and previous transcriptome findings, piglets from the same fetus are selected as models for studying IUGR. The cellular landscape of the liver is created by scRNA-seq to reveal sex-dependent patterns in IUGR-induced hepatic injury. One week after birth, IUGR piglets experience hypoxic stress. IUGR females exhibit fibroblast-driven T cell conversion into an immune-adapted phenotype, which effectively alleviates inflammation and fosters hepatic regeneration. In contrast, males experience even more severe hepatic injury. Prolonged inflammation due to disrupted lipid metabolism hinders intercellular communication among non-immune cells, which ultimately impairs liver regeneration even into adulthood. Additionally, Apolipoprotein A4 (APOA4) is explored as a novel biomarker by reducing hepatic triglyceride deposition as a protective response against hypoxia in IUGR males. PPARα activation can mitigate hepatic damage and meanwhile restore over-expressed APOA4 to normal in IUGR males. The pioneering study offers valuable insights into the sexually dimorphic responses to hepatic injury during IUGR.

Effect of Reduced INR in Early Pregnancy on the Occurrence of Preeclampsia: A Retrospective Cohort Study.

To investigate the effect of reduced early-pregnancy activated partial thrombin time (APTT), prothrombin time (PT), and international standardized ratio (INR) on the risk of preeclampsia. A total of 8549 pregnant women with singleton births were included. Early pregnancy APTT, PT, and INR levels, with age, birth, prepregnancy body mass index, fibrinogen (FBG), thrombin time (TT), D-dimer (DD2), antithrombin III (ATIII), fibrin degradation products (FDP) as confounders, generalized linear model of APTT, the relative risk of PT and INR when INR reduction. After adequate adjustment for confounders, the relative risk of preeclampsia was 0.703 for every 1 s increase in plasma PT results in early pregnancy, and for every 0.1 increase in plasma INR results, the relative risk of preeclampsia was 0.767. With a PT less than the P25 quantile (<11 s), the relative risk of preeclampsia was 1.328. The relative risk of preeclampsia at an INR less than the P25 quantile (<0.92) was 1.24. There was no statistical association between APTT on the risk of preeclampsia. The relative risk of preeclampsia is strongly associated with a decrease in PT and INR in early pregnancy. PT and INR in early pregnancy were a potential marker in the risk stratification of preeclampsia. Focusing on reduced PT and INR levels in early pregnancy can help to identify early pregnancies at risk for preeclampsia.

Effect of N-Carbamylglutamate Supplementation on Growth Performance, Jejunal Morphology, Amino Acid Transporters, and Antioxidant Ability of Weaned Pigs.

Weaning is an important period that affects the performance of piglets. However, the regulation of dietary amino acid levels is considered to be an effective way to alleviate the weaning stress of piglets. N-carbamylglutamate (NCG) plays an important role in improving the growth performance and antioxidant capacity of animals. A total of 36 weaned piglets were randomly assigned to two treatment groups, a control group (CON) and a 500 mg/kg NCG group (NCG), and the experiment lasted for 28 days. The results show that the NCG treatment group showed an increased 0-28 days average weight gain and average daily feed intake, and also increased contents of GLU and HDL, and lower SUN in serum, and an upregulation of the expression of the amino acid transporters SNAT2, EAAC1, SLC3A1, and SLC3A2 mRNA in the jejunum (p < 0.05), as well as an increased villus length and VH:CD ratio, and claudin-1, occludin, and ZO-1 mRNA expression in the jejunum (p < 0.05). The NCG treatment group showed an increased content of GSH-Px in serum and T-AOC and SOD in the jejunum, and a lower content of MDA (p < 0.05); and the upregulation of the mRNA expression related to antioxidant enzymes (CAT, SOD1, Gpx4, GCLC, GCLM and Nrf2, AhR, CYP1A1) in the jejunal mucosa (p < 0.05). In addition, compared with the control group, the NCG treatment group saw an upregulation in the mRNA expression of IL-10 and a decrease in the expression of IL-1ß and IL-4 in the jejunal mucosa (p < 0.05). In summary, the results of this study suggest that NCG improved growth performance and jejunal morphology, improved the jejunal transport of amino acids related to the ornithine cycle, and improved the antioxidant capacity in weaned pigs.

The cognitive effects of adjunctive repetitive transcranial magnetic stimulation for late-onset depression: a randomized controlled trial with 4 week follow-up.

Objectives: Cognitive impairment is common and linked to poor outcomes in patients with late-onset depression (LOD). The cognitive effects of repetitive transcranial magnetic stimulation (rTMS) for LOD are not well understood. This study aimed to investigate the effects of rTMS on cognitive function in elderly patients with LOD. Methods: In total, 58 elderly patients (aged 60 to 75 years) with depression were enrolled and randomly assigned to an active rTMS group or a sham group. The participants received active or sham rTMS over the left dorsolateral prefrontal cortex for 4 weeks, 5 days a week, at a frequency of 10 Hz rTMS and 120% of the motor threshold (MT). Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at baseline, the end of the 4 week treatment period, and at the 4 week follow-up. Results: The active rTMS group showed significant improvements in immediate memory and attention scores on the RBANS compared to the sham group. However, no significant differences were observed between the two groups in other cognitive domains assessed by the RBANS. No serious adverse events related to rTMS treatment were observed. Conclusion: Treatment with 120% MT rTMS was associated with improvement in cognitive defects related to the active phase of LOD. These findings suggest that rTMS could provide early improvements in cognitive function in clinical settings for elderly patients with LOD.Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=40698, identifier ChiCTR1900024445.

Investigation of the relationship between changes in maternal coagulation profile in the first trimester and the risk of developing preeclampsia.

Normal pregnancy is a hypercoagulable state with an increase in coagulation factor levels and a decrease in natural anticoagulation. However, a higher hypercoagulable state with prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), increased D-dimer, and mean platelet volume is seen in women with preeclampsia at the time of onset. In addition, endothelial dysfunction occurs before the clinical symptoms of preeclampsia. Therefore, we undertook this study to investigate the coagulation profile in the first trimester in women who developed preeclampsia later. A total of 853 pregnant women with singleton births at the Obstetrics and Gynecology Hospital of Fudan University between January 2021 and December 2021 were included in this case-control study. In the comparison with the controls (n = 531), the mean value of D-dimer, APTT, thrombin time (TT), antithrombin (AT)), and fibrin degradation products (FDP) was significantly lower in preeclamptic women at the time of diagnosis (n = 322). The changes in the coagulation profile were not associated with the severity or the time of onset. The reduced values of D-dimer, AT, and FDP, and increased values of TT were also observed in the first trimester in women who developed preeclampsia later and were not associated with the severity, or the time of onset of preeclampsia. After adjusting for maternal age and BMI, the values of D-dimer and AT in the first trimester were correlated to the risk of developing preeclampsia. Our findings suggest that there is an abnormal maternal response to the hemostatic system in early gestational age in women who developed preeclampsia later and measuring the coagulation profile could be an additional predictive marker of preeclampsia.

Evaluating the Application Potential of a Recombinant Ganoderma Protein as Bioactive Ingredients in Cosmetics.

The aim of this study was to evaluate the application potential of a recombinant fungal immunomodulatory protein from Ganoderma lucidum (rFIP-glu). First, a recombinant plasmid pPIC9K::FIP-glu-His was transferred into Pichia pastoris for the production of protein. The protein was then to assess its free radical scavenging abilities and the effect on the viability of both human immortalized keratinocytes (HaCaT cells) and mouse B16-F10 melanoma cells (B16 cells) in vitro, followed by the effect on the melanin synthesis of B16 cells. The results of SDS-PAGE and western blot showed that rFIP-glu was successfully expressed. Furtherly, a bioactivity assay in vitro indicated that the scavenging rate of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals reached 84.5% at 6.0 mg/mL (p ≤ 0.0001) of rFIP-glu, showing strong antioxidant activity. Subsequently, a safety evaluation demonstrated that rFIP-glu promoted the proliferation of HaCaT cells, with the cell viability reaching 124.3% at 48 µg/mL (p ≤ 0.01), regarding the cell viability of B16 cells after exposure to rFIP-glu (48 µg/mL) significantly inhibited, to 80.7% (p ≤ 0.01). Besides, rFIP-glu inhibited the melanin synthesis of B16 cells in a dose-dependent manner from 100-1000 µg/mL, and rFIP-glu at 500 µg/mL (p ≤ 0.01) exhibited the highest intracellular melanin amount reduction of 16.8%. Furthermore, a mechanism analysis showed that rFIP-glu inhibited tyrosinase (TYR) activity by up-regulating the expression of the microphthalmia-associated transcription factor (MITF) and down-regulating the gene expression of TYR and tyrosinase-related protein-1 (TYRP-1), thus inhibiting melanin synthesis. The data implied that rFIP-glu had significant antioxidant activity and whitening potency. It should be used as raw materials for cosmeceutical applications.

Nurse-led shared decision-making on complementary therapy use by patients with diabetes: An participatory action research.

AIMS: The aim of this study was to develop, implement and evaluate a nurse-led shared decision-making model of care for discussing the use of complementary and alternative medicine with diabetic patients and to explore to what extent the risk-benefit assessment of using complementary and alternative medicine can provide a framework for facilitating nurse-patient dialogue and strengthening patient involvement in their disease management. DESIGN: Participatory action research with pre-post intervention. METHODS: A two-run cycle of action and spirals from participatory action research was undertaken using a purposive sampling method to involve healthcare professionals and diabetic patients from September 2021 to June 2022. The nurse-led shared decision-making model of care was designed and implemented congruent with participatory action research principles. Quantitative measures were collected about patients' perceived involvement in shared decision-making and their understanding of the risks and benefits of using complementary and alternative medicine. Patients' outcomes of disease control (fasting plasma glucose and HbA1c) were also collected. Data were analysed using IBM SPSS software (version 28). Interviews were summarized using thematic analysis. An EQUATOR Network guideline for participatory action research supported the preparation of this paper. RESULTS: Comparison of pre-post intervention outcomes showed that patients' scale scores on shared decision-making involvement and understanding of the risk-benefit of using complementary and alternative medicine improved significantly after implementing the model. Fasting plasma glucose improved only slightly after a 3-month follow-up. CONCLUSIONS: The care model strengthens patient involvement in their disease management and makes appropriate decisions about CAM use that should reduce potentially harmful side effects or interactions between CAM and conventional medicine. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: The shared decision-making model of care incorporates evidence-based CAM research into practice, facilitates the standardization of CAM management in diabetes, improves care options for patients and educates nurses about CAM use in managing diabetes. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Antinuclear antibody (ANA) status predicts immune-related adverse events in liver cancer patients undergoing anti-PD-1 therapy.

Immune-related adverse events (irAEs) clinically resemble autoimmune diseases, indicating autoantibodies could be potential biomarkers for the prediction of irAEs. This study aimed to assess the predictive value of peripheral blood antinuclear antibody (ANA) status for irAEs, considering the time and severity of irAEs, as well as treatment outcome in liver cancer patients administered anti-PD-1 therapy. Ninety-three patients with advanced primary liver cancer administered anti-PD-1 treatment were analyzed retrospectively. They were divided into the ANA positive (ANA+, titer ≥ 1:100) and negative (ANA-, titer < 1:100) groups. Development of irAEs, progression-free survival (PFS), and overall survival (OS) were assessed. Compared with ANA- patients, ANA+ cases were more prone to develop irAEs (43.3% vs. 19.2%, P = 0.031). With the increase of ANA titers, the frequency of irAEs increased. The time interval between anti-PD-1 therapy and the onset of irAEs was significantly shorter in ANA+ patients compared with the ANA- group (median, 1.7 months vs. 5.0 months, P = 0.022). Moreover, the time between anti-PD-1 therapy and irAE occurrence decreased with increasing ANA titer. In addition, PFS and OS were decreased in ANA+ patients compared with the ANA- group (median PFS, 2.8 months vs. 4.2 months, P = 0.043; median OS, 21.1 months vs. not reached, P = 0.041). IrAEs occur at higher frequency in ANA+ liver cancer patients undergoing anti-PD-1 therapy. ANA titer could help predict irAE development and treatment outcome in these patients.

Genome-Wide Identification of the Q-type C2H2 Transcription Factor Family in Alfalfa (Medicago sativa) and Expression Analysis under Different Abiotic Stresses.

Q-type C2H2 zinc-finger protein (C2H2-ZFP) transcription factors are associated with many plant growth development and environmental stress responses. To date, there have been few analyses of the Q-type C2H2-ZFP gene family in alfalfa (Medicago sativa subsp. sativa). In this study, we identified 58 Q-type C2H2-ZFPs across the entire alfalfa genome, and the gene structure, motif composition, chromosomal mapping, and cis-regulatory elements were explored, as well as the expression profiles of specific tissues and the response under different abiotic stresses. According to their phylogenetic features, these 58 MsZFPs were divided into 12 subgroups. Synteny analysis showed that duplication events play a vital role in the expansion of the MsZFP gene family. The collinearity results showed that a total of 26 and 42 of the 58 MsZFP genes were homologous with Arabidopsis and M. truncatula, respectively. The expression profiles showed that C2H2-ZFP genes played various roles in different tissues and abiotic stresses. The results of subsequent quantitative real-time polymerase chain reaction (qRT-PCR) showed that the nine selected MsZFP genes were rapidly induced under different abiotic stresses, indicating that C2H2-ZFP genes are closely related to abiotic stress. This study provides results on MsZFP genes, their response to various abiotic stresses, and new information on the C2H2 family in alfalfa.

The LPS induced pyroptosis exacerbates BMPR2 signaling deficiency to potentiate SLE-PAH.

Pulmonary arterial hypertension (PAH) is a common and fatal complication of systemic lupus erythematosus (SLE). Whether the BMP receptor deficiency found in the genetic form of PAH is also involved in SLE-PAH patients remains to be identified. In this study, we employed patient-derived samples from SLE-associated PAH (SLE-PAH) and established comparable mouse models to clarify the role of BMP signaling in the pathobiology of SLE-PAH. Firstly, serum levels of LPS and autoantibodies (auto-Abs) directed at BMP receptors were significantly increased in patients with SLE-PAH compared with control subjects, measured by ELISA. Mass cytometry was applied to compare peripheral blood leukocyte phenotype in patients prior to and after treatment with steroids, which demonstrated inflammatory cells alteration in SLE-PAH. Furthermore, BMPR2 signaling and pyroptotic factors were examined in human pulmonary arterial endothelial cells (PAECs) in response to LPS stimulation. Interleukin-8 (IL-8) and E-selectin (SELE) expressions were up-regulated in autologous BMPR2+/R899X endothelial cells and siBMPR2-interfered PAECs. A SLE-PH model was established in mice induced with pristane and hypoxia. Moreover, the combination of endothelial specific BMPR2 knockout in SLE mice exacerbated pulmonary hypertension. Pyroptotic factors including gasdermin D (GSDMD) were elevated in the lungs of SLE-PH mice, and the pyroptotic effects of serum samples isolated from SLE-PAH patients on PAECs were analyzed. BMPR2 signaling upregulator (BUR1) showed anti-pyroptotic effects in SLE-PH mice and PAECs. Our results implied that deficiencies of BMPR2 signaling and proinflammatory factors together contribute to the development of PAH in SLE.

N-Glycosylated Ganoderma lucidum immunomodulatory protein improved anti-inflammatory activity via inhibition of the p38 MAPK pathway.

The global health emergency generated by coronavirus disease-2019 has prompted the search for immunomodulatory agents. There are many potential natural products for drug discovery and development to tackle this disease. One of these candidates is the Ganoderma lucidum fungal immunomodulatory protein (FIP-glu). In the present study, we clarify the influences of N-linked glycans on the improvement of anti-inflammatory activity and the potential mechanisms of action. Four proteins, including FIP-glu (WT) and its mutants N31S, T36N and N31S/T36N, were successfully expressed in P. pastoris, of which T36N and N31S/T36N were glycoproteins. After treatment with peptide-N-glycosidase F, the results of SDS-PAGE and Western blot showed that the glycan moiety was removed completely, indicating that the glycan moiety was N-linked. This was also demonstrated by UPLC-qTOF-MS. The cytotoxicity assay showed that N-linked glycans decreased the cytotoxicity of WT; while, the RT-qPCR assay showed that N-glycosylated WT regulated the mRNA expression of IL-6 and TGF-ß1. The Western blot results showed that N-glycosylated WT reduced the phosphorylation level of p38 MAPK. In conclusion, our findings revealed a novel mechanism by which N-glycosylation of FIP-glu improved its anti-inflammatory activity through the regulation of the expression of inflammatory cytokines in RAW264.7 via inhibition of p38 MAPK phosphorylation. It was proved that N-glycosylation significantly improved the functional properties of FIP-glu, providing theoretical and technical support for expanding the application of FIPs in the food and pharmaceutical industries.

Hepatic Arterial Infusion Chemotherapy with Modified FOLFOX as an Alternative Treatment Option in Advanced Hepatocellular Carcinoma Patients with Failed or Unsuitability for Transarterial Chemoembolization.

OBJECTIVE: This study aimed to assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with modified FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as an alternative treatment option in advanced hepatocellular carcinoma (HCC) patients with failed or unsuitability for transarterial chemoembolization (TACE). MATERIALS AND METHODS: From September 2018 to January 2020, 87 advanced HCC patients who progressed on TACE or were not eligible for TACE received HAIC treatment with modified FOLFOX. The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), tumor response assessed by Response Evaluation Criteria in Solid Tumors 1.1, and adverse events graded according to CTCAE 5.0. Based on prognostic factors determined by multivariate analysis, a nomogram was developed to predict patient survival. RESULTS: The median OS and PFS were 9.0 months (95%CI 7.6-10.4) and 3.7 months (95%CI 3.1-4.3), respectively. The objective response rate was 13.8%, with a disease control rate of 48.3%. Grade 3 adverse events were observed, such as infection (9.2%), thrombocytopenia (5.7%), hyperbilirubinemia (3.4%), abdominal pain (2.3%) and alanine aminotransferase increase (2.3%). Albumin, AST, and extrahepatic metastasis were incorporated to construct a new nomogram that could stratify patients into three prognostic subgroups, including low-, intermediate-, and high-risk groups, with significant differences in 9-month OS rates (71%, 42% and 6%, respectively; p< 0.001). The nomogram was better than the Okuda, AJCC, and CLIP staging systems for OS prediction. CONCLUSION: These findings support the feasibility of HAIC with modified FOLFOX as an alternative treatment strategy for advanced HCC when TACE is ineffective or unsuitable.

Preventive and Therapeutic Spermidine Treatment Attenuates Acute Colitis in Mice.

Inflammatory bowel disease (IBD) is associated with acute and chronic inflammation of the gastrointestinal tract and has emerged to be a global disease. Spermidine, a natural polyamine, plays a critical role in maintaining cellular homeostasis. Herein, we investigated the impact and mechanism of spermidine on both dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis in mice. We found that spermidine exerted protective effects against acute colitis, evidenced by reduced disease activity index (DAI) and colonic inflammation, increased colonic length, and upregulated tight junction proteins in these two colitis models. Importantly, spermidine exerted significant therapeutic and preventive effects against DSS-induced colitis. Pre- and post-treatment with spermidine reduced the expression of proinflammatory cytokines, phosphorylation of (nuclear factor-κB) NF-κB and (mitogen-activated protein kinase) MAPK, and the activation of F4/80 macrophages and T cells in the colon. Furthermore, spermidine upregulated M2 macrophage markers, whereas it downregulated M1 markers in the inflamed colons. In parallel, spermidine reduced M1 pro-inflammatory markers and enhanced M2 anti-inflammatory genes in RAW264.7 cells. These results revealed that spermidine-ameliorated colitis might be through the regulation of M1/M2 macrophage polarization. In addition, spermidine treatment also alleviated LPS/TNF-α-induced inflammation in Caco-2 cells. Taken together, spermidine prevented and reversed colonic inflammation in colitis mice and might be a promising candidate for IBD intervention.

Relationship Between Alzheimer's Disease and Retinal Choroidal Thickness: A Cross-Sectional Study.

BACKGROUND: The choroid is involved directly or indirectly in many pathological conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). OBJECTIVE: The objective of this study was to investigate the association between retinal choroidal properties and the pathology of AD by determining choroidal thickness, hippocampus volume, cognitive functions, and plasma BACE1 activity. METHODS: In this cross-sectional study, 37 patients with AD and 34 age-matched controls were included. Retinal choroidal thickness was measured via enhanced depth imaging optical coherence tomography. Hippocampal volume was measured via 3.0T MRI. Cognitive functions were evaluated using the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog). Plasma BACE1 activity was analyzed using a fluorescence substrate-based plasma assay, and regression model were to analyze the data. RESULTS: Retinal choroidal thickness was significantly thinner in the AD group than in the control group [(114.81±81.30) µm versus (233.79±38.29) µm, p < 0.05]. Multivariable regression analysis indicated that the ADAS-cog scores (ß=-0.772, p = 0.000) and age (ß=-0.176, p = 0.015) were independently associated with choroidal thickness. The logistic regression model revealed that the subfoveal choroidal thickness was a significant predictor for AD (OR = 0.984, 95% CI: 0.972-0.997). CONCLUSION: There was a general tendency of choroid thinning as the cognitive function declined. Although choroidal thickness was not a potential indicator for early stage AD, it was valuable in monitoring AD progression.

WRKY Transcription Factors in Medicago sativa L.: Genome-Wide Identification and Expression Analysis Under Abiotic Stress.

Alfalfa (Medicago sativa L.) is the most widely cultivated leguminous herb in the world. Its agricultural development has been restricted by various adverse environmental conditions, including water deficiency, high salinity, and low temperature. WRKY transcription factors (TFs) serve important roles in the regulation of plant development and stress responses. Research on the WRKY gene family has been reported for several species, but minimal information is available for alfalfa. In the present study, a total of 107 WRKY genes were identified in alfalfa and divided into 3 main groups. The classification, evolution, conserved motifs, and tissue expression were comprehensively analyzed. Meanwhile, 27 MsWRKY candidate genes that may be involved in abiotic stress were isolated through an analysis of gene expression profiles under different stresses, including cold, abscisic acid, drought, and salt treatments. Additionally, investigation of the cis-elements and potential biological functions of these genes further revealed that MsWRKY TFs may serve important roles in multiple stress resistance in alfalfa. This study provides an important foundation for future cloning and functional studies of WRKY genes in alfalfa.

Statistical Optimization of Polysaccharides Production by the Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) in Solid-State Fermentation Using Highland Barley Grains.

Ganoderma lucidum is a widely used medicinal mushroom in traditional Chinese medicine that creates a diverse set of bioactive compounds. Highland barley, a typical nutrition-balanced crop, is not convenient for direct consumption but its nutritional characteristics meet the modern requirements of health food. In the present study, barley grains were used as substrates on solid-state fermentation (SSF) of G. lucidum. Statistical optimization of media composition was employed for enhancing the production of polysaccharides. Peptone, medlar, and KH2PO4 were identified as the most important components for producing polysaccharide. Based on the one-factor-at-a-time experimentation, a quadratic regression model with the polysaccharide contents as the response value was established by central composite design (CCD). The results showed that the predicted variables were 2.38% peptone, 1.14% medlar, and 0.25% KH2PO4 for the maximum yield of predicted polysaccharides of 11.64% in the fermented substrate. The experimental polysaccharides obtained using the predicted optimum media composition constituted 11.61% of the fermented substrate, which validates the high degree of accuracy of optimization for enhanced production of polysaccharides by SSF. This study suggested that in the process of barley grains fermentation by G. lucidum for polysaccharides production, the optimized SSF substrate consists of 71.4% barley grains, 2.38% peptone, 1.14% medlar, 0.25% KH2PO4, 2.5% glucose, 0.25% MgSO4 · 7H2O, and 1% CaCO3. According to this study, the strain G. lucidum 00679 showed a good fermentation property by optimizing the media. It might be a candidate industrial strain for further process optimization and scale-up study.

Optimization of the fermentation parameters for the production of Ganoderma lucidum immunomodulatory protein by Pichia pastoris.

In order to obtain a better fermentation parameter for the production of recombinant Ganoderma lucidum immunomodulatory protein (rFIP-glu), an engineered Pichia pastoris GS115 was investigated on the fermentation time, temperature, methanol concentration and initial pH of media, while immunomodulatory activities of the rFIP-glu was confirmed. L9(33) orthogonal experiment were firstly employed to optimize various fermentation parameters in the shake-flask level. The optimized fermentation parameters were subsequently verified in a 5 L fermenter. Biological activities including cell viability and tumor necrosis factor-alpha (TNF-α) mRNA of the rFIP-glu were evaluated on murine macrophage RAW264.7 cells. The results showed that the yield of rFIP-glu was up to 368.71 µg/ml in the shake-flask, and 613.47 µg/ml in the 5 L fermenter, when the Pichia pastoris was incubated in basic media with the methanol concentration 1.0% and initial pH 6.5, and with constant shaking at 280 rpm for 4 days at 26 °C. In vitro assays of biological activity indicated that rFIP-glu had significant toxicity against RAW264.7 cells, and possessed the ability to induce TNF-α mRNA expression in macrophage RAW264.7 cells. In conclusion, engineered P. pastoris showed a good fermentation property under the optimum fermentation parameters. It could be a candidate industrial strain for further study.

Crystalline amino acids supplementation improves the performance and carcass traits in late-finishing gilts fed low-protein diets.

This study investigated the effects of amino acids (AA) supplementation in low-crude protein (CP) diets on the growth performance and carcass characteristics in late-finishing gilts. Ninety gilts (93.8 ± 5.5 kg) were randomly allotted to one of the five diets which consisted of a normal-CP (137 g/kg) or four low-CP (105 g/kg) diets for 28 days. The low-CP diets were supplemented with lysine + threonine + methionine (LCM), LCM + tryptophan (LCT), LCT + valine (LCV) or LCV + isoleucine (LCI), respectively. Non-significant difference in average daily gain (ADG) was obtained in gilts receiving the control and LCV diet, which was higher than that of gilts fed the LCM diet (p < .05). The additions of crystalline AA in the low-CP diet resulted in the improvements in ADG (linear and quadratic effect, p < .05) and fat-free lean gain (quadratic effect, p < .05) and influenced the valine concentration (linear and quadratic effect, p < .05) and proportion of saturated fatty acid (linear effect, p < .05) in longissimus muscle. The results indicated that the valine supplementation could further improve the performance in 94 to 118 kg gilts fed the 105 g/kg CP diet.

Efficacy of Group Reminiscence Therapy on Cognition, Depression, Neuropsychiatric Symptoms, and Activities of Daily Living for Patients With Alzheimer Disease.

The current study aimed to investigate the effects of group reminiscence therapy on cognitive function, depression, neuropsychiatric symptoms, and activities of daily living in patients with mild-to-moderate Alzheimer disease (AD). A single-blind randomized parallel-design controlled trial was conducted between May 1, 2017, and April 30, 2018. Ninety patients with mild-to-moderate AD recruited from Beijing Geriatric Hospital were randomly allocated into intervention (n = 45) and control groups (n = 45). In the intervention group, group-based reminiscence therapy was performed in two 30- to 45-minute sessions weekly for 12 weeks. Control participants received only conventional drug treatments and routine daily care. Alzheimer disease-related symptoms were evaluated using the Alzheimer's Disease Assessment Scale-Cognitive section, the Cornell Scale for Depression in Dementia (CSDD), the Neuropsychiatric Inventory, and the Barthel Index. Four time points were set for data collection: baseline (before treatment), 4 weeks (during treatment), 12 weeks (end of treatment), and 24 weeks (12 weeks posttreatment). χ2 Tests, independent t tests, repeated-measures analysis of variance, and Bonferroni tests were used for data analysis. Significant improvements in depressive and neuropsychiatric symptoms were found in the intervention group compared to the control group (P < .05). Mean CSDD scores in the intervention group were improved at all 3 time points compared to baseline and showed the greatest effect at 12 weeks (t = 2.076, P = .041) and 24 weeks follow-up (t = 3.834, P = .000) compared to controls. Group reminiscence therapy was effective for improving depressive symptoms and was beneficial for treating neuropsychiatric symptoms in patients with AD.

Ganoderma proteins and their potential applications in cosmetics.

Ganoderma have been regarded as a traditional source of natural bioactive compounds for centuries and have recently been exploited for potential components in the cosmetics industry. Besides Ganoderma polysaccharides and triterpenes, multiple proteins have been found in Ganoderma. With the in-depth study of these proteins, various pharmacological functions of Ganoderma have become important in the discovery and development of new products. In the review, we summarized and discussed the kinds and characteristics of Ganoderma proteins, especially on fungal immunomodulatory proteins (FIPs) which can be potentially developed into cosmeceuticals or nutricosmetics and are a suitable target for production using established biotechnological methods. Furthermore, we discuss their pharmacological activities of the proteins with a focus on their pharmacological functions related to cosmetics, such as antioxidant activity, inhibition of melanin, antibacterial activity, and regulation of inflammatory mediators. Numerous other questions also are addressed before the proteins can be widely accepted and used as cosmetic additives.